The purpose of the Organic Synthesis Core Facility (OSCF) is to provide MSKCC investigators with a fully equipped facility complete with chemistry instrumentation, GMP infrastructure, and staff with the ability to interact with non-chemists as well as chemists, in order to carry out the requested chemical synthesis and consultation. OSCF also assists investigators with pre-clinical and clinical projects. Services are focused on the following: The chemical synthesis of compounds which are not readily available. This is accomplished using established synthetic protocols or by developing new synthetic methodologies. The synthesis of assay development tools and reagents: a) fluorescently labeled compounds, b) affinity labeled compounds, and c) cross linker-tethered molecules. Cold-labeled (13C, 2H, 15N) and radio-labeled (3H, 14C, 1251, 32P, ...etc.) compounds and precursors for preclinical and clinical pharmacological studies which cannot be addressed by the shared Cyclotron- Radiochemistry Core facility. To perform large-scale -cGMP or non-cGMP- chemical syntheses of compounds with demonstrated activity in primary bioassays for preclinical, phase I and II clinical studies (i.e. Le y, Globo H, which are penta- and hexa-carbohydrate antigen vaccine constructs, Cur-61414, peptidyl-Luciferin enzyme activity beacons, and Marimastat) in order to provide sufficient quantities for continued testing. The synthesis of modified and unmodified compounds in amounts that permit their availability for in vitro and in vivo assays and for secondary assays. For example, modifications are introduced to improve solubility, affinity, and specificity. Design, synthesis, and generation of libraries of structurally related compounds based on confirmed hits; library optimization through structure-activity relationships (SAR) identified in a pharmacophore using directed library synthesis and structure-guided design in order to enhance targeting, specificity, and bioavailability while minimizing toxicity.
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